Maurya Santosh Kumar, Chaudhri Smriti, Kumar Shashank, Gupta Sanjay
Molecular Signaling & Drug Discovery Laboratory, Department of Biochemistry, Central University of Punjab, Bathinda, 151401, Punjab, India.
Department of Urology, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH, 44106, USA.
Pharm Res. 2025 Jan;42(1):49-67. doi: 10.1007/s11095-024-03811-1. Epub 2025 Jan 7.
Metabolic alterations are commonly associated with various cancers and are recognized as contributing factors to cancer progression, invasion, and metastasis. Drug repurposing, a strategy in drug discovery, utilizes existing knowledge to recommend established drugs for new indications based on clinical data or biological evidence. This approach is considered a less risky alternative to traditional drug development. Metformin, a biguanide, is a product of Galega officinalis (French lilac) primarily prescribed for managing type 2 diabetes, is recognized for its ability to reduce hepatic glucose production and enhance insulin sensitivity, particularly in peripheral tissues such as muscle. It also improves glucose uptake and utilization while decreasing intestinal glucose absorption. Statins, first isolated from the fungus Penicillium citrinum is another class of medication mainly used to lower cholesterol levels in individuals at risk for cardiovascular diseases, work by inhibiting the enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, which is essential for cholesterol biosynthesis in the liver. Metformin is frequently used in conjunction with statins to investigate their potential synergistic effects. Combination of metformin and simvastatin has gathered much attention in cancer research because of its potential advantages for cancer prevention and treatment. In this review, we analyze the effects of metformin and simvastatin, both individually and in combination, on key cancer hallmarks, and how this combination affects the expression of biomolecules and associated signaling pathways. We also summarize preclinical research, including clinical trials, on the efficacy, safety, and potential applications of repurposing metformin and simvastatin for cancer therapy.
代谢改变通常与各种癌症相关，并被认为是癌症进展、侵袭和转移的促成因素。药物再利用是药物研发中的一种策略，它利用现有知识，根据临床数据或生物学证据推荐已批准药物用于新的适应症。这种方法被认为是一种比传统药物开发风险更小的选择。二甲双胍是一种双胍类药物，是山羊豆（法国丁香）的产物，主要用于治疗2型糖尿病，因其能够减少肝脏葡萄糖生成并增强胰岛素敏感性而闻名，尤其是在肌肉等外周组织中。它还能改善葡萄糖摄取和利用，同时减少肠道葡萄糖吸收。他汀类药物最初是从真菌桔青霉中分离出来的，是另一类主要用于降低心血管疾病风险个体胆固醇水平的药物，其作用机制是抑制3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）还原酶，该酶是肝脏中胆固醇生物合成所必需的。二甲双胍经常与他汀类药物联合使用，以研究它们的潜在协同作用。二甲双胍和辛伐他汀的联合使用在癌症研究中备受关注，因为其在癌症预防和治疗方面具有潜在优势。在这篇综述中，我们分析了二甲双胍和辛伐他汀单独使用及联合使用对关键癌症特征的影响，以及这种联合使用如何影响生物分子的表达和相关信号通路。我们还总结了将二甲双胍和辛伐他汀重新用于癌症治疗的疗效、安全性和潜在应用的临床前研究，包括临床试验。
